AMINOPROPOXYPHENYL AND BENZYL 1-OXA-4,9-DIAZASPIROUNDECANE DERIVATIVES HAVING MULTIMODAL ACTIVITY AGAINST PAIN

Title:

AMINOPROPOXYPHENYL AND BENZYL 1-OXA-4,9-DIAZASPIROUNDECANE DERIVATIVES HAVING MULTIMODAL ACTIVITY AGAINST PAIN

Document Type and Number:

WIPO Patent Application WO/2019/180188

Kind Code:

A1

Abstract:

The present invention relates to aminopropoxyphenyl and benzyl 1-oxa-4,9- diazaspiroundecanederivatives having dual pharmacological activity towards both the α2δ subunit, in particular the α2δ-1 subunit, of the voltage-gated calcium channel and the µ-opioid receptor, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy, in particular for the treatment of pain.

Inventors:

ALMANSA-ROSALES CARMEN (ES)
VIRGILI-BERNADO MARINA (ES)
ALONSO-XALMA MONICA (ES)
OSORIO-PLANES LAURA (ES)

Application Number:

PCT/EP2019/057183

Publication Date:

September 26, 2019

Filing Date:

March 22, 2019

Export Citation:

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Assignee:

ESTEVE PHARMACEUTICALS SA (ES)

International Classes:

C07D498/10; A61K31/537; A61P29/00

Domestic Patent References:

WO2015185207A1	2015-12-10
WO2015185209A1	2015-12-10

Other References:

TURK, D.C.; WILSON, H.D.; CAHANA, A., LANCET, vol. 377, 2011, pages 2226 - 2235
GOLDBERG, D.S.; MCGEE, S.J., BMC PUBLIC HEALTH, vol. 11, 2011, pages 770
ZAMPONI ET AL., PHARMACOL REV., vol. 67, 2015, pages 821 - 70
PERRET; LUO, NEUROTHERAPEUTICS, vol. 6, 2009, pages 679 - 92
NEUMAIER ET AL., PROG NEUROBIOL., vol. 129, 2015, pages 1 - 36
VINK; ALEWOOD, BR J PHARMACOL., vol. 167, 2012, pages 970 - 89
DAVIES ET AL., TRENDS PHARMACOL SCI., vol. 28, 2007, pages 220 - 8
DOLPHIN AC, NAT REV NEUROSCI., vol. 13, 2012, pages 542 - 55
BIOCHIM BIOPHYS ACTA, vol. 1828, 2013, pages 1541 - 9
"Progress in Pain Research and Management", vol. 25, 2003, IASP PRESS, article "Opioids and Pain Relief: A Historical Perspective"
DICKENSON, A.H.; SUZUKI, R.: "Opioids in neuropathic pain: Clues from animal studies", EUR J PAIN, vol. 9, 2005, pages 113 - 6, XP004767581, DOI: doi:10.1016/j.ejpain.2004.05.004
LEHAR ET AL., NAT BIOTECHNOL, vol. 27, 2009, pages 659 - 666
GILRON ET AL., LANCET NEUROL., vol. 12, no. 11, November 2013 (2013-11-01), pages 1084 - 95
SCHRODER ET AL., J PHARMACOL EXP THER., vol. 337, 2011, pages 312 - 20
J PHARMACOL EXP THER., vol. 342, 2012, pages 232
ZHANG ET AL., CELL DEATH DIS., vol. 5, 2014, pages e1138
HOPKINS, NAT CHEM BIOL., vol. 4, 2008, pages 682 - 90
MAO, J.; GOLD, M.S.; BACKONJA, M., J. PAIN, vol. 12, 2011, pages 157 - 166
BORNOT A; BAUER U; BROWN A; FIRTH M; HELLAWELL C; ENGKVIST O: "Systematic Exploration of Dual-Acting Modulators from a Combined Medicinal Chemistry and Biology Perspective", J. MED. CHEM, vol. 56, 2013, pages 1197 - 1210
KROGSGAARD-LARSEN ET AL.: "Textbook of Drug design and Discovery", April 2002, TAYLOR & FRANCIS

Attorney, Agent or Firm:

PETERS, Hajo et al. (DE)

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Claims:

CLAIMS:

1. Compound of general formula (I),

wherein

X is selected from a bond, -[C(R_aRb)]_P-, -[CH₂]pC(0)[CH₂]_q-, -[CH₂]_pC(0)N(R_z)[CH₂]_q-, - [CH₂]_pN(R_z)C(0)[CH₂]_q- and -[CH₂]_pN(R_z)[CH₂]_q-;

R_a is selected from hydrogen, halogen, substituted or unsubstituted Ci-₆ alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl;

R_b is selected from hydrogen, halogen, substituted or unsubstituted Ci-₆ alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; alternatively, R_a and R_b, taken together with the carbon atom to which they are attached, form a substituted or unsubstituted cycloalkyl;

R_z is selected from hydrogen, substituted or unsubstituted Ci-₆ alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl and - C(0)-Ci-6 alkyl; p is 0, 1 , 2, 3, 4 or 5; q is 0, 1 , 2, 3, 4 or 5;

n is 0 or 1 ;

Yi is -C(RioRio')-; wherein R₁₀ and Rio· are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; alternatively, R₁₀ and R-io form, with the carbon atom to which they are attached, a substituted or unsubstituted cycloalkyl;

Y₂ is -C(Rio”Rio )-; wherein Rio- and R-io- are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl; alternatively, R_10” and R-io-form, with the carbon atom to which they are attached, a substituted or unsubstituted cycloalkyl;

wherein m is 0, 1 or 2; r is 0, 1 or 2;

Y is -CH2- or C=0;

R₅ is selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted alkylcycloalkyl;

Re· is selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl;

alternatively, R₅ and R₅· taken together with the carbon atom to which they are attached form a substituted or unsubstituted cycloalkyl;

R₆ is selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl and -C(0)R7;

R₇ is selected from substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl;

Re is selected from hydrogen, halogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl and -ORsi;

Rs· is selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl and substituted or unsubstituted C_2-6 alkynyl;

R₂ is selected from substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl;

R₃ is selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted alkylcycloalkyl;

R_3' is selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, and substituted or unsubstituted C_2-6 alkynyl;

R₄ and R_4' are independently selected from halogen, -R₄I , -OR₄I , -NO₂, -NR_4iR₄r, - NR_4iC(0)R₄r, -NR_4iS(0)₂R₄r, -S(0)₂NR_4iR₄r, -NR_4iC(0)NR₄rR₄-r, -SR₄I , - S(0)R₄I , -S(0)₂R₄I , -CN, haloalkyl, haloalkoxy, -C(0)0R_4i, -C(0)NR_4iR₄r, - 0CH₂CH₂0R₄I , -NR_4iS(0)₂NR_{4i '}R_4i” and -C(CH₃)₂0R₄I ; wherein R₄I , R₄rand R₄r are independently selected from hydrogen, substituted or unsubstituted C_1-6 alkyl, substituted or unsubstituted C_2-6 alkenyl, substituted or unsubstituted C_2-6 alkynyl and substituted or unsubstituted cycloalkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

2. Compound according to claim 1 wherein R₂ is a substituted or unsubstituted group selected from phenyl and thienyl. 3. Compound according to any one of claims 1 or 2 wherein the compound of Formula

(I) is a compound of Formula (I’), (l^a), (l^a’), (l^b), (l^b), (l^c) or (l^c’),

(I^a),

(I^b), 0

371 (l^c) wherein Rg and Rg· are independently selected from halogen, -R21 , -OR21 , -NO2, - NR21 R21’, -NR_2iC(0)R₂r, -NR2iS(0)2R2r, -S(0)2NR2i R2r, - NR2iC(0)NR2i R2i”, - SR21 , -S(0)R2i , -S(0)2R2i , -CN, haloalkyl, haloalkoxy, -C(0)0R2i , -C(0)NR2i R2r, - OCH2CH2OR21 , -NR2iS(0)₂NR₂rR2r' and -C(CH₃)₂OR₂I ; wherein R21 , R21' and R21” are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, and substituted or unsubstituted C2-6 alkynyl;

4. Compound according to any one of claims 1 to 3 wherein

wherein

p is 0, 1 , 2, 3, 4 or 5;

q is 0, 1 , 2, 3, 4 or 5;

and R1 is as defined in the previous claims.

5. Compound according to anyone of claims 1 to 4 wherein X is a bond, C(O),

6. Compound according to any one of claims 1 to 5 wherein

p is 0, 1 , 2, 3, 4 or 5; preferably p is 0, 1 or 2.

7. Compound according to any one of claims 1 to 5 wherein

q is 0, 1 , 2, 3, 4 or 5; preferably q is 0.

8. Compound according to any one of claims 1 to 7 wherein the compound is selected from

or

9. Process for the preparation of compounds of Formula (I) as defined in any one of claims 1 to 8,

a) wherein X represents a bond, and wherein Ri, R₂, R3, R3', R₄, R₄·, Ui, Y2 and n have the meanings as defined in the preceding claims, said process comprises treating a compound of formula (I la),

wherein Q represents chloro, bromo, iodo or triflate, with a suitable /V-containing cyclic reagent of formula (ill-1 )

R₁-H

MI-1 under Buchwald-Hartwig or Ullmann arylation conditions;

or b) wherein -X- represents -[C(R_aRb)]_P-, and wherein R_a, Rt_>, Ri, R2, R3, R3', R₄, R₄·, Ui, Y2 and n and p have the meanings as defined in the preceding claims, said process comprises treating a compound of formula (lib’)

wherein r represents 0 to 4, with a /V-containing cyclic reagent of formula (ill-1 )

R₁-H

MI-1 under standard reductive amination conditions;

or

c) wherein -X- represents -[C(R_aRb)]_P-, and wherein R_a, Rb, R1, R2, R3, R3', R₄, R₄·, Ui, Y2 and n and p have the meanings as defined in the preceding claims, said process comprises treating a compound of formula (I la),

wherein Q represents chloro, bromo, iodo ortriflate, with an organometallic reagent of formula (ill-2’)

P

III-2' wherein M represents a suitable organometallic group, preferably a boron or zinc reagent, and p has the meaning as defined in the preceding claims;

or d) wherein -X- represents -[CR_aR_b]_PC(0)[CH₂]q- and q is 0, and wherein R_a and R_b are hydrogen and wherein Ri, R₂, R3, R3', R₄, R₄·, Yi, Y2, n, p and q have the meanings as defined in the preceding claims, said process comprises treating a compound of formula (lie’)

with a /V-containing cyclic reagent of formula (ill-1 )

R₁-H

MI-1 under conventional amidation conditions;

or e) wherein -X- represents -[CR_aR_b]_PN(R_z)C(0)[CH₂]q-, and wherein R_a and R_b are hydrogen and wherein R1, R₂, R3, R3', R₄, R₄·, Yi, Y2 , n, p and q have the meanings as defined in the preceding claims, said process comprises treating a compound of formula (VI’)

wherein LG represents a leaving group such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate, p, q and Rz have the meanings as defined in thepreceding claims, with a /V-containing cyclic reagent of formula (ill-1 )

R₁-H

HI-1 under conventional alkylation conditions;

or

f) wherein -X- represents -[CR_aRb]pN(R_z)C(0)[CH2]q-, and wherein R_a and Rb are hydrogen and wherein Ri, R₂, R3, R3', R₄, R₄·, Yi, Y2, n, p and q have the meanings as defined in the preceding claims, said process comprises treating an amino compound of formula (lid’)

wherein p and Rz have the meanings as defined in the preceding claims, with an acyl reagent of formula (ill-3),

z '

MI-3 under amidation conditions, wherein Z represents OH or halogen and q has the meaning as defined in the preceding claims;

or g) wherein -X- represents -[CR_aR_b]pN(R_z)C(0)[CH₂]q-, p is 0, and wherein R_a and R_b are hydrogen and wherein Ri, R₂, R₃, R_3', R₄, R₄·, Y₁, Y₂ , n, p and q have the meanings as defined in the preceding claims, said process comprises reacting a compound of formula (I la)

wherein Q represents chloro, bromo, iodo ortriflate, with a carboxamido compound of formula (ill-5)

under Ullmann arylation conditions, wherein q and Rz have the meanings as defined in the preceding claims; or

h) wherein n is 0, and wherein R₁, R₂, R₃, R_3', R₄, R₄·, X, Y₁ and Y₂ have the meanings as defined in the preceding claims, said process comprises reacting a compound of formula (Vila) wherein G is OH,

Vila with an alkylating agent of formula (VIII) wherein Z represents a leaving group such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate;

or

i) wherein n is 0, and wherein Ri, R₂, R3, R3', R₄, R₄·, X, Y1 and Y₂ have the meanings as defined in the preceding claims, said process comprises reacting a compound of formula (Vila) wherein G is OH,

Vila with an alcoholof formula (VIII) wherein Z represents OH, in the presence of a suitable azo compound;

or

j) wherein n is 0, and wherein Ri, R₂, R3, R3', R₄, R₄·, X, Y1 and Y₂ have the meanings as defined in the preceding claims, said process comprises reacting a compound of formula (Vila) wherein G is halogen,

Vila with an alcohol of formula (VIII) wherein Z represents OH in the presence of a strong base,;

or k) wherein n is 1 , and wherein Ri, R₂, R₃, R_3', R₄, R₄·, X, Y1 and Y₂ have the meanings as defined in the preceding claims, said process comprises reacting a compound of formula (VI lb)

with an agent of formula (VIII), wherein either Z represents OH and G represents a leaving group such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate, or alternatively Z represents a leaving group such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate and G represents OH.

10. Use of a compound of Formula II, lla, Ila-LG, lib, Mb’, llb-LG, llb’-LG, lie, lie’, lie-

LG, llc’-LG, lid, lid’, lld-LG, Ild’-LG, ill-1 , ill-2, MI -2, ill-3, ill-4, III-5, IVa, IVb, IVb’, IVc, IVc’, IVd, IVd’, IVe, IVf, V, VI, VI’, VII, Vila, Vllb, VIII, VIII-LG, IX, X, X’, X-LG, X’-LG, XI, XI-LG, XI’ or XI’-LG

XI'-LG wherein R_a, Rb, Ri, R2, R3, R3', R₄, R₄·, Ui, Y2 , n, p, q, r and R_z have the meanings as defined in the preceding claims, Q represents chloro, bromo, iodo or triflate, LG represents a leaving group such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate, have the meanings as defined in the description, M represents a suitable organometallic group, Z represents OH or halogen, and G is OH, halogen or a leaving group such as chloro, bromo, iodo, mesylate, tosylate, nosylate or triflate, for the preparation of compounds of Formula (I).

1 1. A pharmaceutical composition which comprises a compound of Formula (I) as defined in any one of claims 1 to 8 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant or vehicle.

12. A compound of Formula (I) as defined in any one of claims 1 to 8 for use as a medicament.

13. A compound of Formula (I) as defined in any one of claims 1 to 8 for use as a medicament; preferably for use as a medicament for the treatment of pain, especially medium to severe pain, visceral pain, chronic pain, cancer pain, migraine, inflammatory pain, acute pain or neuropathic pain, allodynia or hyperalgesia.

Description:

AMINOPROPOXYPHENYL AND BENZYL 1 -OXA-4,9- DIAZASPIROUNDECANE DERIVATIVES HAVING MULTIMODAL ACTIVITY AGAINST PAIN

FIELD OF THE INVENTION

The present invention relates to compounds having dual pharmacological activity towards both the a ₂d subunit of the voltage-gated calcium channel, and the m-opioid receptor (MOR or mu-opioid receptor) and more particularly to aminopropoxyphenyl and benzyl 1 -oxa-4,9-diazaspiroundecane derivatives having this pharmacological activity, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy, in particular for the treatment of pain.

BACKGROUND OF THE INVENTION

The adequate management of pain constitutes an important challenge, since currently available treatments provide in many cases only modest improvements, leaving many patients unrelieved (Turk, D.C., Wilson, H.D., Cahana, A.; 201 1 ; Lancet ; 377; 2226- 2235). Pain affects a big portion of the population with an estimated prevalence of 20 % and its incidence, particularly in the case of chronic pain, is increasing due to the population ageing. Additionally, pain is clearly related to comorbidities, such as depression, anxiety and insomnia, which leads to important productivity losses and socio-economical burden (Goldberg, D.S., McGee, S.J.; 201 1 ; BMC Public Health] 1 1 ; 770). Existing pain therapies include non-steroidal anti-inflammatory drugs (NSAIDs), opioid agonists, calcium channel blockers and antidepressants, but they are much less than optimal regarding their safety ratio. All of them show limited efficacy and a range of secondary effects that preclude their use, especially in chronic settings.

Voltage-gated calcium channels (VGCC) are required for many key functions in the body. Different subtypes of voltage-gated calcium channels have been described (Zamponi et al., Pharmacol Rev. 2015 67:821 -70). The VGCC are assembled through interactions of different subunits, namely oti (Ca _voti), b (Ca _vp) a ₂d (Ca _va ₂6) and g (Ca _vy). The o i subunits are the key porous forming units of the channel complex, being responsible for the Ca ²⁺ conduction and generation of Ca ²⁺ influx. The a2d, b, and g subunits are auxiliary, although very important for the regulation of the channel, since they increase the expression of the oti subunits in the plasma membrane as well as modulate their function, resulting in functional diversity in different cell types. Based on their physiological and pharmacological properties, VGCC can be subdivided into low voltage-activated T-type (Ca _v3.1 , Ca _v3.2, and Ca _v3.3), and high voltage-activated L- (Ca _v1 .1 through Ca _v1 .4), N-(Ca _v2.2), P/Q-(Ca _v2.1 ), and R-(Ca _v2.3) types, depending on the channel forming Cava subunits. All of these five subclasses are found in the central and peripheral nervous systems. Regulation of intracellular calcium through activation of these VGCC plays obligatory roles in: 1 ) neurotransmitter release, 2) membrane depolarization and hyperpolarization, 3) enzyme activation and inactivation, and 4) gene regulation (Perret and Luo, Neurotherapeutics. 2009 6:679-92; Zamponi et al., 2015 supra ; Neumaier et al., Prog Neurobiol. 2015 129:1 -36.). A large body of data has clearly indicated that VGCC are implicated in mediating various disease states including pain processing. Drugs interacting with the different calcium channel subtypes and subunits have been developed. Current therapeutic agents include drugs targeting L-type Ca _v1 .2 calcium channels, particularly 1 ,4-dihydropyridines, which are widely used in the treatment of hypertension. T-type (Ca _v3) channels are the target of ethosuximide, widely used in absence epilepsy. Ziconotide, a peptide blocker of N-type (Ca _v2.2) calcium channels, has been approved as a treatment of intractable pain. (Perret and Luo, 2009, supra, Vink and Alewood, Br J Pharmacol. 2012 167:970-89.).

The Ca _v1 and Ca _v2 subfamilies contain an auxiliary a d subunit, which is the therapeutic target of the gabapentinoid drugs of value in certain epilepsies and chronic neuropathic pain. To date, there are four known a d subunits, each encoded by a unique gene and all possessing splice variants. Each a d protein is encoded by a single messenger RNA and is post-translationally cleaved and then linked by disulfide bonds. Four genes encoding a2d subunits have now been cloned. a ₂d-1 was initially cloned from skeletal muscle and shows a fairly ubiquitous distribution. The a ₂d-2 and a ₂d-3 subunits were subsequently cloned from brain. The most recently identified subunit, a ₂d-4, is largely non-neuronal. The human a ₂d-4 protein sequence shares 30, 32 and 61 % identity with the human a ₂d-1 , a ₂d-2 and a ₂d-3 subunits, respectively. The gene structure of all a ₂d subunits is similar. All a ₂d subunits show several splice variants (Davies et al., Trends Pharmacol Sci. 2007 28:220-8.; Dolphin AC, Nat Rev Neurosci. 2012 13:542-55., Biochim Biophys Acta. 2013 1828:1541 -9.). The Ca _vot ₂5-1 subunit may play an important role in neuropathic pain development (Perret and Luo, 2009, supra ; Vink and Alewood, 2012, supra). Biochemical data have indicated a significant Ca _vot ₂5-1 , but not Ca _vot ₂5-2, subunit upregulation in the spinal dorsal horn, and DRG (dorsal root ganglia) after nerve injury that correlates with neuropathic pain development. In addition, blocking axonal transport of injury-induced DRG Ca _vot ₂5-1 subunit to the central presynaptic terminals diminishes tactile allodynia in nerve injured animals, suggesting that elevated DRG Ca _vot ₂5-1 subunit contributes to neuropathic allodynia.

The Ca _vot ₂5-1 subunit (and the Ca _vot ₂5-2, but not Ca _vot ₂5-3 and Ca _vot ₂5-4, subunits) is the binding site for gabapentin which has anti-allodynic/ hyperalgesic properties in patients and animal models. Because injury-induced Ca _vot ₂5-1 expression correlates with neuropathic pain development and maintenance, and various calcium channels are known to contribute to spinal synaptic neurotransmission and DRG neuron excitability, injury-induced Ca _vot ₂5-1 subunit upregulation may contribute to the initiation and maintenance of neuropathic pain by altering the properties and/or distribution of VGCC in the subpopulation of DRG neurons and their central terminals, therefore modulating excitability and/or synaptic neuroplasticity in the dorsal horn. Intrathecal antisense oligonucleotides against the Ca _vot ₂5-1 subunit can block nerve injury-induced Ca _vot ₂5-1 upregulation and prevent the onset of allodynia and reserve established allodynia.

As mentioned above, the 0, ₂6 subunits of VGCC form the binding site for gabapentin and pregabalin, which are structural derivatives of the inhibitory neurotransmitter GABA although they do not bind to GABAA, GABAB, or benzodiazepine receptors, or alter GABA regulation in animal brain preparations. The binding of gabapentin and pregabalin to the Ca _vot ₂5 subunit results in a reduction in the calcium-dependent release of multiple neurotransmitters, leading to efficacy and tolerability for neuropathic pain management. Gabapentinoids may also reduce excitability by inhibiting synaptogenesis (Perret and Luo, 2009, supra, Vink and Alewood, 2012, supra, Zamponi et al., 2015, supra).

As mentioned before, there are few available therapeutic classes for the treatment of pain, and opioids are among the most effective, especially when addressing severe pain states. They act through three different types of opioid receptors (mu, kappa and gamma) which are transmembrane G-protein coupled receptors (GPCRs). Still, the main analgesic action is attributed to the activation of the m-opioid receptor (MOR). However, the general administration of MOR agonists is limited due to their important side effects, such as constipation, respiratory depression, tolerance, emesis and physical dependence [Meldrum, M.L. (Ed.)· Opioids and Pain Relief: A Historical Perspective. Progress in Pain Research and Management, Vol 25. IASP Press, Seattle, 2003]. Additionally, MOR agonists are not optimal for the treatment of chronic pain as indicated by the diminished effectiveness of morphine against chronic pain conditions. This is especially proven for the chronic pain conditions of neuropathic or inflammatory origin, in comparison to its high potency against acute pain. The finding that chronic pain can lead to MOR down-regulation may offer a molecular basis for the relative lack of efficacy of morphine in long-term treatment settings [Dickenson, A.H., Suzuki, R. Opioids in neuropathic pain: Clues from animal studies. Eur J Pain 9, 1 13-6 (2005)]. Moreover, prolonged treatment with morphine may result in tolerance to its analgesic effects, most likely due to treatment-induced MOR down-regulation, internalization and other regulatory mechanisms. As a consequence, long-term treatment can result in substantial increases in dosing in order to maintain a clinically satisfactory pain relief, but the narrow therapeutic window of MOR agonists finally results in unacceptable side effects and poor patient compliance.

Polypharmacology is a phenomenon in which a drug binds multiple rather than a single target with significant affinity. The effect of polypharmacology on therapy can be positive (effective therapy) and/or negative (side effects). Positive and/or negative effects can be caused by binding to the same or different subsets of targets; binding to some targets may have no effect. Multi-component drugs or multi-targeting drugs can overcome toxicity and other side effects associated with high doses of single drugs by countering biological compensation, allowing reduced dosage of each compound or accessing context-specific multitarget mechanisms. Because multitarget mechanisms require their targets to be available for coordinated action, one would expect synergies to occur in a narrower range of cellular phenotypes given differential expression of the drug targets than would the activities of single agents. In fact, it has been experimentally demonstrated that synergistic drug combinations are generally more specific to particular cellular contexts than are single agent activities, such selectivity is achieved through differential expression of the drugs’ targets in cell types associated with therapeutic, but not toxic, effects (Lehar et al., Nat Biotechnol 2009; 27: 659-666.). In the case of chronic pain, which is a multifactorial disease, multi-targeting drugs may produce concerted pharmacological intervention of multiple targets and signaling pathways that drive pain. Because they actually make use of biological complexity, multi-targeting (or multi-component drugs) approaches are among the most promising avenues toward treating multifactorial diseases such as pain (Gilron et al., Lancet Neurol. 2013 Nov;12(1 1 ):1084-95.). In fact, positive synergistic interaction for several compounds, including analgesics, has been described (Schroder et al., J Pharmacol Exp Ther. 201 1 ; 337:312-20. Erratum in: J Pharmacol Exp Ther. 2012; 342:232.; Zhang et al., Cell Death Dis. 2014; 5:e1 138.; Gilron et al., 2013, supra).

Given the significant differences in pharmacokinetics, metabolisms and bioavailability, reformulation of drug combinations (multi-component drugs) is challenging. Further, two drugs that are generally safe when dosed individually cannot be assumed to be safe in combination. In addition to the possibility of adverse drug-drug interactions, if the theory of network pharmacology indicates that an effect on phenotype may derive from hitting multiple targets, then that combined phenotypic perturbation may be efficacious or deleterious. The major challenge to both drug combination strategies is the regulatory requirement for each individual drug to be shown to be safe as an individual agent and in combination (Hopkins, Nat Chem Biol. 2008; 4:682-90.).

An alternative strategy for multitarget therapy is to design a single compound with selective polypharmacology (multi-targeting drug). It has been shown that many approved drugs act on multiple targets. Dosing with a single compound may have advantages over a drug combination in terms of equitable pharmacokinetics and biodistribution. Indeed, troughs in drug exposure due to incompatible pharmacokinetics between components of a combination therapy may create a low-dose window of opportunity where a reduced selection pressure can lead to drug resistance. In terms of drug registration, approval of a single compound acting on multiple targets faces significantly lower regulatory barriers than approval of a combination of new drugs (Hopkins, 2008, supra).

Thus, the present application, relates to the advantages of having dual activity, for m- receptor and the a ₂d-1 subunit of voltage-gated calcium channels, in the same molecule to treat chronic pain. In this way, the present invention relates to compounds having a complementary dual mechanism of action (m-receptor agonist and blocker of the a ₂d subunit, in particular the a ₂d-1 subunit, of voltage-gated calcium channels) which implies a better profile of tolerability than the strong opioids (morphine, oxycodone, fentanyl etc) and/or better efficacy and tolerability than gabapentinoids (pregabalin and gabapentin).

Pain is multimodal in nature, since in nearly all pain states several mediators, signaling pathways and molecular mechanisms are implicated. Consequently, monomodal therapies fail to provide complete pain relief. Currently, combining existing therapies is a common clinical practice and many efforts are directed to assess the best combination of available drugs in clinical studies (Mao, J., Gold, M.S., Backonja, M.; 201 1 ; J. Pain; 12; 157-166).

Accordingly, there is still a need to find compounds that have an alternative or improved pharmacological activity in the treatment of pain, being both effective and showing the desired selectivity, and having good“drugability” properties, i.e. good pharmaceutical properties related to administration, distribution, metabolism and excretion.

The authors of the present invention, have found a serie of compounds that show dual pharmacological activity towards both the a ₂d subunit, in particular the a ₂d-1 subunit, of the voltage-gated calcium channel, and the m-opioid receptor (MOR or mu-opioid receptor) resulting in an innovative, effective and alternative solution for the treatment of pain.

In view of the existing results of the currently available therapies and clinical practices, the present invention offers a solution by combining in a single compound binding to two different targets relevant for the treatment of pain. This was mainly achieved by providing the compounds according to the invention that bind both to the m-opioid receptor and to the a ₂d subunit, in particular the a ₂d-1 subunit, of the voltage-gated calcium channel.

SUMMARY OF THE INVENTION

In this invention a family of structurally distinct aminopropoxyphenyl and benzyl 1 -oxa- 4,9-diazaspiroundecane derivatives, encompassed by formula (I), which have a dual pharmacological activity towards both the a ₂d subunit, in particular the a ₂d-1 subunit, of the voltage-gated calcium channel, and the m-opioid receptor, was identified thus solving the above problem of identifying alternative or improved pain treatments by offering such dual compounds. The main object of the invention is directed to a compound having a dual activity binding to the a ₂d subunit, in particular the a ₂d-1 subunit, of the voltage-gated calcium channel and the m-opioid receptor for use in the treatment of pain.

As this invention is aimed at providing a compound or a chemically related series of compounds which act as dual ligands of the a ₂d subunit, in particular the a ₂d-1 subunit, of the voltage-gated calcium channel and the m-opioid receptor it is a very preferred embodiment if the compound has a binding expressed as K, responding to the following scales:

K _ί(m) is preferably < 1000 nM, more preferably < 500 nM, even more preferably < 100 nM.

K,(a ₂d-1 ) is preferably < 10000 nM, more preferably < 5000 nM, even more preferably

< 500 nM or even more preferably < 100 nM.

The invention is directed in a main aspect to a compound of general Formula (I),

wherein Ri, R ₂, R3, R3', R ₄, R ₄·, X, Ui, Y2 and n are as defined below in the detailed description.

A further object of the invention refers to the processes for preparation of compounds of general formula (I). A still further object of the invention refers to the use of intermediate compounds for the preparation of a compound of general formula (I).

It is also an object of the invention a pharmaceutical composition comprising a compound of formula (I). Finally, it is an object of the invention the use of compound as a medicament and more particularly for the treatment of pain and pain related conditions.

DETAILED DESCRIPTION OF THE INVENTION

In this invention a family of structurally distinct aminopropoxyphenyl and benzyl 1-oxa- 4,9-diazaspiroundecane derivatives, encompassed by formula (I), which have a dual pharmacological activity towards both the a ₂d subunit, in particular the a ₂d-1 subunit, of the voltage-gated calcium channel, and the m-opioid receptor was identified, thus solving the above problem of identifying alternative or improved pain treatments by offering such dual compounds. The main object of the invention is directed to a compound having a dual activity binding to the a ₂d subunit, in particular the a ₂d-1 subunit, of the voltage-gated calcium channel and the m-opioid receptor, for use in the treatment of pain.

As this invention is aimed at providing a compound or a chemically related series of compounds which act as dual ligands of the a ₂d subunit, in particular the a ₂d-1 subunit, of the voltage-gated calcium channel and the m-opioid receptor, it is a very preferred embodiment if the compound has a binding expressed as K, responding to the following scales:

K _ί(m) is preferably < 1000 nM, more preferably < 500 nM, even more preferably < 100 nM.

K,(a ₂d-1 ) is preferably < 10000 nM, more preferably < 5000 nM, even more preferably

< 500 nM or even more preferably < 100 nM.

The applicant has surprisingly found that the problem of providing a new effective and alternative for treating pain and pain related disorders can be solved by using a multimodal balanced analgesic approach combining two different synergistic activities in a single drug (i.e., dual ligands which are bifunctional and bind to m-opioid receptor and to a ₂d subunit, in particular the a ₂d-1 subunit, of the voltage-gated calcium channel), thereby enhancing through the a ₂d blockade without increasing the undesirable side effects. This supports the therapeutic value of a dual agent, whereby the a ₂d binding component acts as an intrinsic adjuvant of the MOR binding component.

A dual compound that possess binding to both the m-opioid receptor and to the a ₂d subunit of the voltage-gated calcium channel shows a highly valuable therapeutic potential by achieving an outstanding analgesia (enhanced in respect to the potency of the opioid component alone) with a reduced side-effect profile (safety margin increased compared to that of the opioid component alone) versus existing opioid therapies.

Advantageously, the dual compounds according to the present invention would in addition show one or more the following functionalities: blockade of the a ₂d subunit, in particular the a ₂d-1 subunit, of the voltage-gated calcium channel and m-opioid receptor agonism

It has to be noted, though, that functionalities“antagonism” and“agonism” are also sub- divided in their effect into subfunctionalities like partial agonism or inverse agonism. Accordingly, the functionalities of the compound should be considered within a relatively broad bandwidth.

An antagonist blocks or dampens agonist-mediated responses. Known subfunctionalities are neutral antagonists or inverse agonists.

An agonist increases the activity of the receptor above its basal level. Known subfunctionalities are full agonists, or partial agonists.

In addition, the two mechanisms complement each other since MOR agonists are only marginally effective in the treatment of neuropathic pain, while the blockers of the a ₂d subunit, in particular the a ₂d-1 subunit, of voltage-gated calcium channels show outstanding effects in preclinical neuropathic pain models. Thus, the a ₂d component, in particular the a ₂d-1 component, adds unique analgesic actions in opioid-resistant pain. Finally, the dual approach has clear advantages over MOR agonists in the treatment of chronic pain as lower and better tolerated doses would be needed based on the potentiation of analgesia but not of the adverse events of MOR agonists. A further advantage of using designed multiple ligands is a lower risk of drug-drug interactions compared to cocktails or multi-component drugs, thus involving simpler pharmacokinetics and less variability among patients. Additionally, this approach may improve patient compliance and broaden the therapeutic application in relation to monomechanistic drugs, by addressing more complex aetiologies. It is also seen as a way of improving the R&D output obtained using the“one drug-one target” approach, which has been questioned over the last years [Bornot A, Bauer U, Brown A, Firth M, Hellawell C, Engkvist O. Systematic Exploration of Dual-Acting Modulators from a Combined Medicinal Chemistry and Biology Perspective. J. Med. Chem, 56, 1 197-1210 (2013)].

In its broader aspect, the present invention is directed to compounds of general Formula (I):

wherein

X is selected from a bond, -[C(R _aRb)] _P-, -[CH ₂]pC(0)[CH ₂] _q-, -[CH ₂] _pC(0)N(R _z)[CH ₂] _q-, - [CH ₂] _pN(R _z)C(0)[CH ₂] _q- and -[CH ₂] _pN(R _z)[CH ₂] _q-;

R _a is selected from hydrogen, halogen, substituted or unsubstituted Ci- ₆ alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; Rb is selected from hydrogen, halogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl; alternatively, R _a and R _b, taken together with the carbon atom to which they are attached, form a substituted or unsubstituted cycloalkyl;

R _z is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl and - C(0)-Ci-6 alkyl; p is 0, 1 , 2, 3, 4 or 5; q is 0, 1 , 2, 3, 4 or 5;

n is 0 or 1 ;

Yi is -C(RioRio')-; wherein R ₁₀ and Rio· are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; alternatively, R ₁₀ and Rio· may form, with the carbon atom to which they are attached, a substituted or unsubstituted cycloalkyl;

Y ₂ is -C(Rio”Rio )-; wherein Rio- and R-io- are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; alternatively, R _10” and Rio- may form, with the carbon atom to which they are attached, a substituted or unsubstituted cycloalkyl;

wherein m is 0, 1 or 2; r is 0, 1 or 2;

Y is -CH ₂- or C=0;

R ₅ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted alkylcycloalkyl;

Re· is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

alternatively, R ₅ and R ₅· taken together with the carbon atom to which they are attached form a substituted or unsubstituted cycloalkyl; R6 is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl and -C(0)R7;

R ₇ is selected from substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl;

Re is selected from hydrogen, halogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl and -ORsi;

Rs· is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; wherein Rei is selected from hydrogen, or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

R ₂ is selected from substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl,

R ₃ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted alkylcycloalkyl;

R _3' is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

R ₄ and R _4' are independently selected from halogen, -R ₄I , -OR ₄I , -NO ₂, -NR _4iR ₄r, - NR _4iC(0)R ₄r, -NR _4iS(0) ₂R ₄r, -S(0) ₂NR _4iR ₄r, -NR _4iC(0)NR ₄rR ₄-r, -SR ₄I , - S(0)R ₄I , -S(0) ₂R ₄I , -CN, haloalkyl, haloalkoxy, -C(0)0R _4i, -C(0)NR _4iR ₄r, - 0CH2CH20R ₄I , -NR _4iS(0)2NR _{4i '}R _4i” and -C(CH3)20R ₄I ; wherein R ₄I , R ₄rand R ₄r are independently selected from hydrogen, substituted or unsubstituted Ci- ₆ alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl and substituted or unsubstituted cycloalkyl;

These compounds according to the invention are optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

Please note that“or a corresponding salt thereof does also mean“or a corresponding pharmaceutically acceptable salt thereof”. This does apply to all below described embodiments and uses of“salt” being thus equivalent to“pharmaceutically acceptable salt”.

In another embodiment, these compounds according to the invention are optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof.

In a particular embodiment the following proviso applies: when Y is CO, then R ₆ is not -C(0)R ₇.

In a particular embodiment the following proviso applies: when R ₆ is -C(0)R ₇, then Y is not CO.

In a particular embodiment the following proviso applies: when R6 is -C(0)R7, then Y is -CH2-. In a further embodiment the compound according to the invention is a compound of general Formula (I)

wherein

X is selected from a bond, -[C(R _aRb)] _P-, -[CH ₂]pC(0)[CH ₂] _q-, -[CH ₂] _pC(0)N(R _z)[CH ₂] _q-, - [CH ₂] _pN(R _z)C(0)[CH ₂] _q- and -[CH ₂] _pN(R _z)[CH ₂] _q-;

R _a is selected from hydrogen, halogen, substituted or unsubstituted Ci- ₆ alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

R _b is selected from hydrogen, halogen, substituted or unsubstituted Ci- ₆ alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; alternatively, R _a and R _b, taken together with the carbon atom to which they are attached, form a substituted or unsubstituted cycloalkyl;

R _z is selected from hydrogen, substituted or unsubstituted Ci- ₆ alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl and - C(0)-Ci-6 alkyl; p is 0, 1 , 2, 3, 4 or 5; q is 0, 1 , 2, 3, 4 or 5;

n is 0 or 1 ;

Yi is -C(RioRio')-; wherein Rio and Rio· are independently selected from hydrogen, substituted or unsubstituted Ci- ₆ alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; alternatively, R ₁₀ and Rio· may form, with the carbon atom to which they are attached, a substituted or unsubstituted cycloalkyl;

Y2 is -C(Rio”Rio'”)-; wherein Rio- and R-io- are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; alternatively, R _10” and Rio- may form, with the carbon atom to which they are attached, a substituted or unsubstituted cycloalkyl;

wherein m is 0, 1 or 2; r is 0, 1 or 2;

Y is -CH2- or C=0;

R5 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted alkylcycloalkyl;

Re· is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

alternatively, R5 and Rs· taken together with the carbon atom to which they are attached form a substituted or unsubstituted cycloalkyl;

wherein the alkyl, alkenyl or alkynyl defined in R ₅ and R ₅· if substituted, is substituted with one or more substituent/s selected from -OR ₅₁, halogen, -CN, haloalkyl, haloalkoxy and -NRsiRsr;

wherein the cycloalkyl, as defined in R ₅, also in alkylcycloalkyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R ₅₁, -OR ₅₁, -NO2, -NR51R51', -NR _5iC(0)R ₅r, -NR5iS(0)2R5r, -S(0)2NR5iR5-r,

NR _5iC(0)NR ₅rR ₅r', -SR ₅₁ , -S(0)Rsi, -S(0) ₂R _SI , -CN, haloalkyl, haloalkoxy, - C(0)OR ₅I , -C(0)NR _5i R ₅ , -OCH ₂CH ₂OR ₅I , -NR _5iS(0) ₂NR ₅rR ₅r and -

C(CH3)20R5i; preferably selected from halogen, -R51, -OR51, -NR51R51', -CN, haloalkyl and haloalkoxy; wherein R ₅₁, Rsr and R ₅r are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, and substituted or unsubstituted C2-6 alkynyl;

wherein the cycloalkyl, as defined in R5-R5', if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R52, -OR52, -NO2, -NR52R52', - NR ₅₂C(0)R _52', -NR ₅₂S(0) ₂R52', -S(0) ₂NR ₅₂R52', - NR ₅₂C(0)NR _52'R _52”, -SR ₅₂ , - S(0)R52, -S(0)2R52, -CN, haloalkyl, haloalkoxy, -C(0)0Rs2, -C(0)NR ₅₂R52·, - OCH2CH2OR52, -NR ₅₂S(0)2NR _52'R52” and -C(CH3)20R52; preferably selected from halogen, -R52, -OR52, -NR52R52', -CN, haloalkyl and haloalkoxy; wherein R52, R52' and R52” are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, and substituted or unsubstituted C2-6 alkynyl;

R6 is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl and -C(0)R7; wherein the alkyl, alkenyl or alkynyl defined in R6, if substituted, is substituted with one or more substituent/s selected from -OR ₆₁, halogen, -CN, haloalkyl, haloalkoxy and -NR61R6I'; wherein the cycloalkyl, aryl or heterocyclyl defined in R6, also in alkylcycloalkyl, alkylaryl and alkylheterocyclyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R61, -OR61, -NO2, -NR6iR6r, -NR6iC(0)R6r, - NR6iS(0)2R6r, -S(0) ₂NR _6iR ₆r, - NR6iC(0)NR6i'R6i”, -SR61 , -S(0)R6i, -S(0)2R6i, -CN, haloalkyl, haloalkoxy, -C(0)0R6i, -C(0)NR6iR6r, -OCH2CH2OR61, - NR6iS(0) ₂NR ₆rR6r and -C(CH3)20R6i; preferably selected from halogen, -R61, - OR61, -NR61R6I', -CN, haloalkyl and haloalkoxy; wherein R61, Rer and R ₆r are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

R7 is selected from substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl; wherein the alkyl, alkenyl or alkynyl defined in R ₇, if substituted, is substituted with one or more substituent/s selected from -OR71, halogen, -CN, haloalkyl, haloalkoxy and -N R71 R71 '; wherein the cycloalkyl, aryl and heterocyclyl, as defined in R ₇, also in alkylcycloalkyl, alkylaryl and alkylheterocyclyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R71, -OR71, -NO2, -NR _7iR ₇r, - NR _7iC(0)R ₇r, -NR7iS(0)2R7 , -S(0)2NR7iR7r, - NR7iC(0)NR7-rR7-r, -SR71 , - S(0)R7i, -S(0)2R7i, -CN, haloalkyl, haloalkoxy, -C(0)0R7i, -C(0)NR _7iR7r, - OCH2CH2OR71, -NR7iS(0) ₂NR ₇rR7r' and -C(CH3)20R7i; preferably selected from halogen, -R71, -OR71, -NR71R71', -CN, haloalkyl and haloalkoxy; wherein R ₇₁, R ₇r and R ₇r are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl; Re is selected from hydrogen, halogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl and -ORsi;

Rs· is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl; wherein the alkyl, alkenyl or alkynyl defined in Re or Re·, if substituted, is substituted with one or more substituent/s selected from -ORsi, halogen, -CN, haloalkyl, haloalkoxy and -NReiRsr; wherein Rei and Rsr are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl;

R ₂ is selected from substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl, wherein the aryl or heterocyclyl in R ₂, if substituted, is substituted with one or more substituent/s selected from halogen, -R21, -OR21, -NO2, -NR21R21', - NR _2iC(0)R ₂r, -NR2iS(0)2R2 , -S(0)2NR2iR2r, - NR2iC(0)NR2i R2i”, -SR21 , - S(0)R2i, -S(0)2R2i, -CN, haloalkyl, haloalkoxy, -C(0)0R2i, -C(0)NR2iR2r, - OCH2CH2OR21, -NR2iS(0) ₂NR ₂rR2r' and -C(CH ₃) ₂OR ₂I ; wherein R21, R21' and R21” are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, and substituted or unsubstituted C2-6 alkynyl;

R ₃ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted alkylcycloalkyl; wherein, the alkyl, alkenyl or alkynyl defined in R ₃, if substituted, is substituted with one or more substituent/s selected from -OR ₃₁, halogen, -CN, haloalkyl, haloalkoxy and -NR31R31'; wherein the cycloalkyl in R ₃, also in alkylcycloalkyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R ₃₁, -OR31, -NO2, -NR31R31', -NR _3iC(0)R ₃r, -NR3iS(0)2R3r, -S(0)2NR3i R3r, - N R ₃₁ C(0)N R ₃₁ R _{31 "}, -SR ₃₁ , -S(0)R ₃I , -S(0) ₂R ₃I , -CN, haloalkyl, haloalkoxy, -C(0)0R3i, -C(0)NR3iR3r, -OCH2CH2OR31,

NR3iS(0) ₂NR ₃rR3r and -C(CH3)20R3i; preferably selected from halogen, - R31, -OR31, -NR31R31', -CN, haloalkyl and haloalkoxy; wherein R ₃₁, R _31' and R _31” are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

R _3' is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl; wherein, the alkyl, alkenyl or alkynyl defined in R _3', if substituted, is substituted with one or more substituent/s selected from -OR ₃₂, halogen, -CN, haloalkyl, haloalkoxy and -NR32R32'; wherein R ₃₂ and R _32' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

R ₄ and R _4' are independently selected from halogen, -R ₄I , -OR ₄I , -NO ₂, -NR _4iR ₄r, - NR _4iC(0)R ₄r, -NR _4iS(0) ₂R ₄r, -S(0) ₂NR _4iR ₄r, -NR _4iC(0)NR ₄rR ₄-r, -SR ₄I , - S(0)R ₄I , -S(0) ₂R ₄I , -CN, haloalkyl, haloalkoxy, -C(0)0R _4i, -C(0)NR _4iR ₄r, - 0CH ₂CH ₂0R _4I , -NR _4iS(0) ₂NR _{4i '}R _4i” and -C(CH ₃) ₂0R _4I ; wherein R ₄₁, R ₄rand R ₄r are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl and substituted or unsubstituted cycloalkyl;

the alkyl, alkenyl or alkynyl, also in alkylaryl, alkylheterocyclyl or al kylcycloal kyl , if substituted and the substitution has not been defined otherwise, it is substituted with one or more substituent/s selected from =0, -OR ₁₃, halogen, -CN, haloalkyl, haloalkoxy and -NR13R13'; wherein R ₁₃ and R _13' are independently selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl, and unsubstituted C _2-6 alkynyl;

the aryl, heterocyclyl or cycloalkyl, also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, if substituted and the substitution has not been defined otherwise, it is substituted with one or more substituent/s selected from =0, halogen, -R-u, -OR ₁₄, -NO2, -NR14R14', -NRl ₄C(0)Rl4·, -NRl4S(0)2Rl4’, -S(0) ₂NRl ₄Rl4',

NRi ₄C(0)NRi4'Ri4”, -SR14 , -S(0)Ri4, -S(0)2Ri4, -CN, haloalkyl, haloalkoxy, - C(0)0Ri4, -C(0)NRi ₄Ri4', -OCH2CH2OR14, -NRi ₄S(0) ₂NRi4'Ri4” and -C(CH3)20Ri4; wherein R-u, Ri _b and R-u- are independently selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl, unsubstituted C _2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl;

optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof. In a further embodiment the compound according to the invention of general Formula (I) is a compound of general Formula (I )

O ^’) wherein Ri, R ₂, R3, R3', R ₄, R ₄·, X and n are as defined in the detailed description, optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound of general Formula (I )

O ^’) wherein

X is selected from a bond, -[C(R _aRb)] _P-, -[CH ₂]pC(0)[CH ₂] _q-, -[CH ₂] _pC(0)N(R _z)[CH ₂] _q-, - [CH ₂] _pN(R _z)C(0)[CH ₂] _q- and -[CH ₂] _pN(R _z)[CH ₂] _q-; R _a is selected from hydrogen, halogen, substituted or unsubstituted Ci- ₆ alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl;

Rb is selected from hydrogen, halogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl; alternatively, R _a and R _b, taken together with the carbon atom to which they are attached, may form a substituted or unsubstituted cycloalkyl;

R _z is selected from hydrogen, substituted or unsubstituted C alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl and - C(0)-Ci-6 alkyl; p is 0, 1 , 2, 3, 4 or 5; q is 0, 1 , 2, 3, 4 or 5;

n is 0 or 1 ;

wherein m is 0, 1 or 2; r is 0, 1 or 2;

Y is -CH2- or C=0;

R ₅ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted alkylcycloalkyl;

Re· is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

alternatively, R ₅ and R ₅· taken together with the carbon atom to which they are attached form a substituted or unsubstituted cycloalkyl;

R ₆ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl and -C(0)R7; wherein R ₇ is selected from substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl; Re is selected from hydrogen, halogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl and -ORsi;

Rs· is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; wherein Rei is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

R ₂ is selected from substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl,

R ₃ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted alkylcycloalkyl;

R _3' is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

R ₄ and R _4' are independently selected from halogen, -R ₄I , -OR ₄I , -NO ₂, -NR _4iR ₄r, - NR _4iC(0)R ₄r, -NR _4iS(0) ₂R ₄r, -S(0) ₂NR _4iR ₄r, -NR _4iC(0)NR ₄rR ₄-r, -SR ₄I , - S(0)R ₄I , -S(0) ₂R ₄I , -CN, haloalkyl, haloalkoxy, -C(0)0R _4i, -C(0)NR _4iR ₄r, - 0CH ₂CH ₂0R ₄I , -NR _4iS(0) ₂NR _{4i '}R _4i” and -C(CH ₃) ₂0R ₄I ; wherein R ₄I , R ₄rand R ₄r are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl and substituted or unsubstituted cycloalkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound of general Formula (I )

(0 wherein

X is selected from a bond, -[C(R _aRb)] _P-, -[CH ₂]pC(0)[CH ₂] _q-, -[CH ₂] _pC(0)N(R _z)[CH ₂] _q-, - [CH ₂] _pN(R _z)C(0)[CH ₂] _q- and -[CH ₂] _pN(R _z)[CH ₂] _q-; R _a is selected from hydrogen, halogen, substituted or unsubstituted Ci- ₆ alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

R _b is selected from hydrogen, halogen, substituted or unsubstituted Ci- ₆ alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; alternatively, R _a and R _b, taken together with the carbon atom to which they are attached, form a substituted or unsubstituted cycloalkyl; R _z is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl and - C(0)-Ci-6 alkyl; p is 0, 1 , 2, 3, 4 or 5; q is 0, 1 , 2, 3, 4 or 5;

n is 0 or 1 ;

wherein m is 0, 1 or 2; r is 0, 1 or 2;

Y is -CH ₂- or C=0;

R5 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted alkylcycloalkyl; Rs· is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

alternatively, R ₅ and R ₅· taken together with the carbon atom to which they are attached form a substituted or unsubstituted cycloalkyl;

wherein the alkyl, alkenyl or alkynyl defined in R ₅ and Rs· if substituted, is substituted with one or more substituent/s selected from -OR ₅₁, halogen, -CN, haloalkyl, haloalkoxy and -NRsiRsr;

wherein the cycloalkyl, as defined in R ₅, also in alkylcycloalkyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R _5I , -OR ₅₁, -NO2, -NR51R51', -NR _5iC(0)R ₅r, -NR5iS(0)2R5r, -S(0)2NR5iR5-r,

NR _5iC(0)NR ₅rR ₅r', -SR ₅₁ , -S(0)Rsi, -S(0) ₂R _SI , -CN, haloalkyl, haloalkoxy, - C(0)0R _5I , -C(0)NR _5i R ₅ , -OCH ₂CH ₂OR _5I , -NR _5iS(0) ₂NR ₅rR _5i and -

C(CH3)20R5i; preferably selected from halogen, -R51, -OR51, -NR51R51', -CN, haloalkyl and haloalkoxy; wherein R ₅₁, Rsr and Rsr are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

wherein the cycloalkyl, as defined in R5-R5', if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R52, -OR52, -NO2, -NR52R52', - NR ₅₂C(0)R _52', -NR ₅₂S(0) ₂R52', -S(0) ₂NR ₅₂R52', - NR ₅₂C(0)NR _52'R _52”, -SR ₅₂ , - S(0)R52, -S(0)2R52, -CN, haloalkyl, haloalkoxy, -C(0)0Rs2, -C(0)NR ₅₂Rs2', - OCH2CH2OR52, -NR ₅₂S(0)2NR _52'R52” and -C(CH3)20R52; preferably selected from halogen, -R52, -OR52, -NR52R52', -CN, haloalkyl and haloalkoxy; wherein R ₅₂, R _52' and R _52” are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

R6 is selected from hydrogen, substituted or unsubstituted Ci-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl and -C(0)R7; wherein the alkyl, alkenyl or alkynyl defined in R6, if substituted, is substituted with one or more substituent/s selected from -OR ₆₁, halogen, -CN, haloalkyl, haloalkoxy and -NR61R6I'; wherein the cycloalkyl, aryl or heterocyclyl defined in R6, also in alkylcycloalkyl, alkylaryl and alkylheterocyclyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R61, -OR61, -NO2, -NR6iR6r, -NR6iC(0)R6r, - NR6iS(0)2R6r, -S(0) ₂NR _6iR ₆r, - NR6iC(0)NR6i'R6i”, -SR61 , -S(0)R6i, -S(0)2R6i, -CN, haloalkyl, haloalkoxy, -C(0)0R6i, -C(0)NR6iR6r, -OCH2CH2OR61, - NR6iS(0) ₂NR ₆rR6r' and -C(CH3)20R6i; preferably selected from halogen, -R61, - OR61, -NR61R6I', -CN, haloalkyl and haloalkoxy; wherein R ₆₁, Rer and Rer are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl;

R ₇ is selected from substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl; wherein the alkyl, alkenyl or alkynyl defined in R ₇, if substituted, is substituted with one or more substituent/s selected from -OR ₇₁, halogen, -CN, haloalkyl, haloalkoxy and -N R71 R71 '; wherein the cycloalkyl, aryl and heterocyclyl, as defined in R ₇, also in alkylcycloalkyl, alkylaryl and alkylheterocyclyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R71, -OR71, -NO2, -NR71R71’, - NR _7iC(0)R ₇r, -NR7iS(0)2R7 , -S(0)2NR7iR7r, - NR7iC(0)NR7-rR7-r, -SR71 , - S(0)R7i, -S(0)2R7i, -CN, haloalkyl, haloalkoxy, -C(0)0R7i, -C(0)NR _7iR7r, - OCH2CH2OR71, -NR _7iS(0) ₂NR7rR7i” and -C(CH3)20R7i; preferably selected from halogen, -R ₇₁, -OR ₇₁, -NR ₇₁R _71', -CN, haloalkyl and haloalkoxy; wherein R ₇₁, R ₇r and R ₇r are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

Re is selected from hydrogen, halogen, substituted or unsubstituted Ci- ₆ alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl and -ORsi;

Rs· is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; wherein the alkyl, alkenyl or alkynyl defined in Re or Re·, if substituted, is substituted with one or more substituent/s selected from -ORsi, halogen, -CN, haloalkyl, haloalkoxy and -NRsiRsr; wherein Rei and Rsr are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

R2 is selected from substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl, wherein the aryl or heterocyclyl in R ₂, if substituted, is substituted with one or more substituent/s selected from halogen, -R21, -OR21, -NO2, -NR21R21', - NR _2iC(0)R ₂r, -NR2iS(0)2R2 , -S(0)2NR2iR2r, - NR2iC(0)NR2i R2i”, -SR21 , - S(0)R2i, -S(0)2R2i, -CN, haloalkyl, haloalkoxy, -C(0)0R2i, -C(0)NR2iR2r, - OCH2CH2OR21, -NR2iS(0) ₂NR ₂rR2r' and -C(CH ₃) ₂OR ₂I ; wherein R21, R21' and R21” are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, and substituted or unsubstituted C2-6 alkynyl;

R3 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted alkylcycloalkyl; wherein, the alkyl, alkenyl or alkynyl defined in R3, if substituted, is substituted with one or more substituent/s selected from -OR31 , halogen, -CN, haloalkyl, haloalkoxy and -N R31 R31'; wherein the cycloalkyl in R3, also in alkylcycloalkyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R31, -OR31, -NO2, -NR31R31', -NR _3iC(0)R ₃r, -NR3iS(0)2R3r, -S(0)2NR3i R3r, - N R31 C(0)N R31 R31 ", -SR31 , -S(0)R ₃I , -S(0) ₂R ₃I , -CN, haloalkyl, haloalkoxy, -C(0)0R3i, -C(0)NR3iR3r, -OCH2CH2OR31,

NR3iS(0) ₂NR ₃rR3r' and -C(CH3)20R3i; preferably selected from halogen, - R31, -OR31, -NR31R31', -CN, haloalkyl and haloalkoxy; wherein R ₃₁, R _31' and R _31” are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

R _3' is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl; wherein, the alkyl, alkenyl or alkynyl defined in R _3', if substituted, is substituted with one or more substituent/s selected from -OR ₃₂, halogen, -CN, haloalkyl, haloalkoxy and -NR32R32'; wherein R ₃₂ and R _32' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

R ₄ and R _4' are independently selected from halogen, -R ₄I , -OR ₄I , -NO ₂, -NR _4iR ₄r, - NR _4iC(0)R ₄r, -NR _4iS(0) ₂R ₄r, -S(0) ₂NR _4iR ₄r, -NR _4iC(0)NR ₄rR ₄-r, -SR ₄I , - S(0)R ₄I , -S(0) ₂R ₄I , -CN, haloalkyl, haloalkoxy, -C(0)0R _4i, -C(0)NR _4iR ₄r, - 0CH ₂CH ₂0R ₄I , -NR _4iS(0) ₂NR _{4i '}R _4i” and -C(CH ₃) ₂0R ₄I ; wherein R ₄I , R ₄rand R ₄rare independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl and substituted or unsubstituted cycloalkyl;

the alkyl, alkenyl or alkynyl, also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, if substituted and the substitution has not been defined otherwise, it is substituted with one or more substituent/s selected from =0, -OR ₁₃, halogen, -CN, haloalkyl, haloalkoxy and -NR13R13'; wherein R ₁₃ and R _13' are independently selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl, and unsubstituted C _2-6 alkynyl;

the aryl, heterocyclyl or cycloalkyl, also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, if substituted and the substitution has not been defined otherwise, it is substituted with one or more substituent/s selected from =0, halogen, -R-u, -OR-u, -NO2, -NR14R14', -NRl ₄C(0)Rl4·, -NRl4S(0)2Rl4’, -S(0) ₂NRl ₄Rl4',

NRi ₄C(0)NRi4'Ri4”, -SR14 , -S(0)Ri4, -S(0)2Ri4, -CN, haloalkyl, haloalkoxy, - C(0)0Ri4, -C(0)NRi ₄Ri4', -OCH2CH2OR14, -NRi ₄S(0) ₂NRi4'Ri4” and -C(CH3)20R-i4; wherein R-u, Ri _b and R-u- are independently selected from hydrogen, unsubstituted

C _1-6 alkyl, unsubstituted C _2-6 alkenyl, unsubstituted C _2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl;

optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound of general Formula (l ^a)

(l ^a)

wherein Ri, R3, R3', R ₄, R ₄·, R9, RET, X, Ui, Y2 and n are as defined in the detailed description, optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound of general Formula (l ^a)

wherein

X is selected from a bond, -[C(R _aRb)] _P-, -[CH ₂]pC(0)[CH ₂] _q-, -[CH ₂] _pC(0)N(R _z)[CH ₂] _q-, - [CH ₂] _pN(R _z)C(0)[CH ₂] _q- and -[CH ₂] _pN(R _z)[CH ₂] _q-; R _a is selected from hydrogen, halogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl;

Rb is selected from hydrogen, halogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl; alternatively, R _a and R _b, taken together with the carbon atom to which they are attached, form a substituted or unsubstituted cycloalkyl;

R _z is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl and - C(0)-Ci-6 alkyl; p is 0, 1 , 2, 3, 4 or 5; q is 0, 1 , 2, 3, 4 or 5;

n is 0 or 1 ;

Yi is -C(RioRio')-; wherein R10 and Rio· are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl; alternatively, R10 and Rio· may form, with the carbon atom to which they are attached, a substituted or unsubstituted cycloalkyl;

Y ₂ is -C(Rio”Rio )-; wherein Rio- and R-io- are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; alternatively, R _10” and Rio- may form, with the carbon atom to which they are attached, a substituted or unsubstituted cycloalkyl;

wherein m is 0, 1 or 2; r is 0, 1 or 2;

Y is -CH2- or C=0;

R ₅ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted alkylcycloalkyl;

Re· is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; alternatively, R ₅ and Rs· taken together with the carbon atom to which they are attached form a substituted or unsubstituted cycloalkyl;

R6 is selected from hydrogen, substituted or unsubstituted Ci-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl and -C(0)R7;

R ₇ is selected from substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl;

Re is selected from hydrogen, halogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl and -ORsi;

Rs· is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl; wherein Rei is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl; R ₃ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted alkylcycloalkyl;

R _3' is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

R ₄ and R _4' are independently selected from halogen, -R ₄I , -OR ₄I , -NO2, -NR _4iR ₄r, - NR _4iC(0)R ₄r, -NR _4iS(0) ₂R ₄r, -S(0) ₂NR _4iR ₄r, -NR _4iC(0)NR ₄rR ₄-r, -SR ₄I , - S(0)R ₄I , -S(0) ₂R ₄I , -CN, haloalkyl, haloalkoxy, -C(0)0R _4i, -C(0)NR _4iR ₄r, - 0CH ₂CH ₂0R ₄I , -NR _4iS(0) ₂NR _{4i '}R _4i” and -C(CH ₃) ₂0R ₄I ; wherein R ₄I , R ₄rand R ₄r are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl and substituted or unsubstituted cycloalkyl;

Rg and Rg· are independently selected from halogen, -R21, -OR21, -NO2, -NR21R21', - NR _2iC(0)R ₂r, -NR2iS(0)2R2 , -S(0)2NR2iR2r, - NR2iC(0)NR2i R2i”, -SR21 , - S(0)R2i, -S(0)2R2i, -CN, haloalkyl, haloalkoxy, -C(0)0R2i, -C(0)NR2iR2r, - OCH2CH2OR21, -NR2iS(0) ₂NR ₂rR2r' and -C(CH ₃) ₂OR ₂I ; wherein R21, R21' and R21” are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, and substituted or unsubstituted C2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof. In a further embodiment the compound according to the invention of general Formula (I) is a compound of general Formula (l ^a)

wherein

X is selected from a bond, -[C(R _aRb)] _P-, -[CH ₂]pC(0)[CH ₂] _q-, -[CH ₂] _pC(0)N(R _z)[CH ₂] _q-, - [CH ₂] _pN(R _z)C(0)[CH ₂] _q- and -[CH ₂] _pN(R _z)[CH ₂] _q-;

R _a is selected from hydrogen, halogen, substituted or unsubstituted C alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

R _b is selected from hydrogen, halogen, substituted or unsubstituted C alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; alternatively, R _a and R _b, taken together with the carbon atom to which they are attached, form a substituted or unsubstituted cycloalkyl;

R _z is selected from hydrogen, substituted or unsubstituted Ci- ₆ alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl and - C(0)-Ci-6 alkyl; p is 0, 1 , 2, 3, 4 or 5; q is 0, 1 , 2, 3, 4 or 5;

n is 0 or 1 ;

Yi is -C(RioRio')-; wherein R ₁₀ and Rio· are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; alternatively, R ₁₀ and Rio· may form, with the carbon atom to which they are attached, a substituted or unsubstituted cycloalkyl;

Y ₂ is -C(Rio”Rio )-; wherein Rio- and R-io- are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; alternatively, R _10” and Rio- may form, with the carbon atom to which they are attached, a substituted or unsubstituted cycloalkyl;

wherein m is 0, 1 or 2; r is 0, 1 or 2;

Y is -CH2- or C=0;

R5 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted alkylcycloalkyl;

Re· is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

alternatively, R5 and Rs· _, taken together with the carbon atom to which they are attached, form a substituted or unsubstituted cycloalkyl;

wherein the alkyl, alkenyl or alkynyl defined in R ₅ and R ₅· if substituted, is substituted with one or more substituent/s selected from -OR ₅₁, halogen, -CN, haloalkyl, haloalkoxy and -NRsiRsr;

wherein the cycloalkyl, as defined in R ₅, also in alkylcycloalkyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R ₅₁, -OR ₅₁, -NO2, -NR51R51', -NR _5iC(0)R ₅r, -NR5iS(0)2R5r, -S(0)2NR5iR5-r,

NR _5iC(0)NR ₅rR ₅r', -SR ₅₁ , -S(0)Rsi, -S(0) ₂R _SI , -CN, haloalkyl, haloalkoxy, - C(0)OR ₅I , -C(0)NR _5i R ₅ , -OCH ₂CH ₂OR ₅I , -NR _5iS(0) ₂NR ₅rR ₅r and - C(CH3)20R5i; preferably selected from halogen, -R51, -OR51, -NR51R51', -CN, haloalkyl and haloalkoxy; wherein R ₅₁, Rsr and Rsr are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

wherein the cycloalkyl, as defined in R ₅-R _5', if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R52, -OR52, -NO2, -NR52R52', - NR ₅₂C(0)R _52', -NR ₅₂S(0) ₂R52', -S(0) ₂NR ₅₂R52', - NR ₅₂C(0)NR _52'R _52”, -SR ₅₂ , - S(0)R52, -S(0)2R52, -CN, haloalkyl, haloalkoxy, -C(0)0Rs2, -C(0)NR ₅₂R52·, - OCH2CH2OR52, -NR ₅₂S(0)2NR _52'R52” and -C(CH3)20R52; preferably selected from halogen, -R52, -OR52, -NR52R52', -CN, haloalkyl and haloalkoxy; wherein R ₅₂, R _52' and R _52” are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

R6 is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl and -C(0)R7; wherein the alkyl, alkenyl or alkynyl defined in R6, if substituted, is substituted with one or more substituent/s selected from -OR ₆₁, halogen, -CN, haloalkyl, haloalkoxy and -NR61R6I'; wherein the cycloalkyl, aryl or heterocyclyl defined in R6, also in alkylcycloalkyl, alkylaryl and alkylheterocyclyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R61, -OR61, -NO2, -NR6iR6r, -NR6iC(0)R6r, - NR6iS(0)2R6r, -S(0) ₂NR _6iR ₆r, - NR6iC(0)NR6i'R6i”, -SR61 , -S(0)R6i, -S(0)2R6i, -CN, haloalkyl, haloalkoxy, -C(0)0R6i, -C(0)NR6iR6r, -OCH2CH2OR61, - NR6iS(0) ₂NR ₆rR6r' and -C(CH3)20R6i; preferably selected from halogen, -R61, - OR61, -NR61R6I', -CN, haloalkyl and haloalkoxy; wherein R ₆₁, Rer and R6i” are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl;

R ₇ is selected from substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl; wherein the alkyl, alkenyl or alkynyl defined in R ₇, if substituted, is substituted with one or more substituent/s selected from -OR ₇₁, halogen, -CN, haloalkyl, haloalkoxy and -NR71R71'; wherein the cycloalkyl, aryl and heterocyclyl, as defined in R ₇, also in alkylcycloalkyl, alkylaryl and alkylheterocyclyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R71, -OR71, -NO2, -NR _7i R ₇r, - NR _7iC(0)R ₇r, -NR7iS(0)2R7 , -S(0)2NR7iR7r, - NR7iC(0)NR7-rR7-r, -SR71 , - S(0)R7i, -S(0)2R7i, -CN, haloalkyl, haloalkoxy, -C(0)0R7i, -C(0)NR _7iR7r, - OCH2CH2OR71, -NR7iS(0) ₂NR ₇rR7r' and -C(CH3)20R7i; preferably selected from halogen, -R71, -OR71, -NR71R71', -CN, haloalkyl and haloalkoxy; wherein R ₇₁, R _71' and R ₇r are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

Re is selected from hydrogen, halogen, substituted or unsubstituted Ci- ₆ alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl and -ORsi;

Rs· is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; wherein the alkyl, alkenyl or alkynyl defined in Re or Re·, if substituted, is substituted with one or more substituent/s selected from -ORsi, halogen, -CN, haloalkyl, haloalkoxy and -NRsiRsr; wherein Rsi and Rsr are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

R ₃ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted alkylcycloalkyl; wherein, the alkyl, alkenyl or alkynyl defined in R ₃, if substituted, is substituted with one or more substituent/s selected from -OR ₃₁, halogen, -CN, haloalkyl, haloalkoxy and -NR31R31'; wherein the cycloalkyl in R ₃, also in alkylcycloalkyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R ₃₁, -OR31, -NO2, -NR31R31', -NR _3iC(0)R ₃r, -NR3iS(0)2R3r, -S(0)2NR3i R3r, - N R ₃₁ C(0)N R ₃₁ R _{31 "}, -SR ₃₁ , -S(0)R _3I , -S(0) ₂R _3I , -CN, haloalkyl, haloalkoxy, -C(0)0R3i, -C(0)NR3iR3r, -OCH2CH2OR31,

NR3iS(0) ₂NR ₃rR3r' and -C(CH3)20R3i; preferably selected from halogen, - R31, -OR31, -NR31R31', -CN, haloalkyl and haloalkoxy; wherein R ₃₁, R _31' and R _31” are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

R _3' is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl; wherein, the alkyl, alkenyl or alkynyl defined in R _3', if substituted, is substituted with one or more substituent/s selected from -OR ₃₂, halogen, -CN, haloalkyl, haloalkoxy and -NR32R32'; wherein R ₃₂ and R _32' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

R ₄ and R _4' are independently selected from halogen, -R _4I , -OR _4I , -NO ₂, -NR _4iR ₄r, - NR _4iC(0)R ₄r, -NR _4iS(0) ₂R ₄r, -S(0) ₂NR _4iR ₄r, -NR _4iC(0)NR ₄rR ₄-r, -SR _4I , - S(0)R _4I , -S(0) ₂R _4I , -CN, haloalkyl, haloalkoxy, -C(0)0R _4i, -C(0)NR _4iR ₄r, - 0CH ₂CH ₂0R _4I , -NR _4iS(0) ₂NR _4i'R _4i” and -C(CH ₃) ₂0R _4I ; wherein R _4I , R ₄rand R ₄r are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl and substituted or unsubstituted cycloalkyl;

Rg and Rg· are independently selected from halogen, -R21, -OR21, -NO2, -NR21R21', - NR _2iC(0)R ₂r, -NR2iS(0)2R2 , -S(0)2NR2iR2 , - NR2iC(0)NR2i R2i”, -SR21 , - S(0)R2i, -S(0)2R2i, -CN, haloalkyl, haloalkoxy, -C(0)OR2i, -C(0)NR _2iR ₂r, - OCH2CH2OR21, -NR2iS(0) ₂NR ₂rR2r' and -C(CH ₃) ₂OR ₂I ; wherein R ₂₁, R _21' and R _21” are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

the alkyl, alkenyl or alkynyl, also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, if substituted and the substitution has not been defined otherwise, it is substituted with one or more substituent/s selected from =0, -OR ₁₃, halogen, -CN, haloalkyl, haloalkoxy and -NR13R13'; wherein R ₁₃ and R _13' are independently selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl, and unsubstituted C _2-6 alkynyl;

the aryl, heterocyclyl or cycloalkyl, also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, if substituted and the substitution has not been defined otherwise, it is substituted with one or more substituent/s selected from =0, halogen, -R-u, -OR14, -NO2, -NR14R14', -NRl ₄C(0)Rl4', -NRl4S(0)2Rl4’, -S(0) ₂NRl ₄Rl4',

NRi ₄C(0)NRi4'Ri4”, -SR14 , -S(0)Ri4, -S(0)2Ri4, -CN, haloalkyl, haloalkoxy, - C(0)0Ri4, -C(0)NRi ₄Ri4', -OCH2CH2OR14, -NRi ₄S(0) ₂NRi4'Ri4” and -C(CH3)20Ri4; wherein R-u, R-u and R-u- are independently selected from hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl, unsubstituted C2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof. In a further embodiment the compound according to the invention of general Formula (I) is a compound of general Formula (l ^a’)

wherein Ri, R3, R3', R ₄, R ₄·, R9, R9', X and n are as defined in the detailed description, optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound of general Formula (l ^a’)

wherein

X is selected from a bond, -[C(R _aRb)] _P-, -[CH ₂]pC(0)[CH ₂] _q-, -[CH ₂] _pC(0)N(R _z)[CH ₂] _q-, - [CH ₂] _pN(R _z)C(0)[CH ₂] _q- and -[CH ₂] _pN(R _z)[CH ₂] _q-;

R _a is selected from hydrogen, halogen, substituted or unsubstituted Ci- ₆ alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

R _b is selected from hydrogen, halogen, substituted or unsubstituted Ci- ₆ alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; alternatively, R _a and R _b, taken together with the carbon atom to which they are attached, may form a substituted or unsubstituted cycloalkyl;

R _z is selected from hydrogen, substituted or unsubstituted Ci- ₆ alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl and - C(0)-Ci-6 alkyl; p is 0, 1 , 2, 3, 4 or 5; q is 0, 1 , 2, 3, 4 or 5; n is 0 or 1 ;

wherein m is 0, 1 or 2; r is 0, 1 or 2;

Y is -CH ₂- or C=0;

R5 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted alkylcycloalkyl;

Re· is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl;

alternatively, R5 and R ₅·, taken together with the carbon atom to which they are attached, form a substituted or unsubstituted cycloalkyl; R6 is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl and -C(0)R7;

R ₇ is selected from substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl;

Re is selected from hydrogen, halogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl and -ORsi;

Rs· is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; wherein Rei is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

R ₃ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted alkylcycloalkyl;

R _3' is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl; R ₄ and R _4' are independently selected from halogen, -R _4I , -OR _4I , -NO2, -NR _4iR ₄r, - NR _4iC(0)R ₄r, -NR _4iS(0) ₂R ₄r, -S(0) ₂NR _4iR ₄r, -NR _4iC(0)NR ₄rR ₄-r, -SR _4I , - S(0)R _4I , -S(0) ₂R _4I , -CN, haloalkyl, haloalkoxy, -C(0)0R _4i, -C(0)NR _4iR ₄r, - 0CH ₂CH ₂0R _4I , -NR _4iS(0) ₂NR _{4i '}R _4i” and -C(CH ₃) ₂0R _4I ; wherein R _4I , R ₄rand R ₄rare independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl and substituted or unsubstituted cycloalkyl;

Rg and Rg· are independently selected from halogen, -R21, -OR21, -NO2, -NR21R21', -

NR _2iC(0)R ₂r, -NR2iS(0)2R2r, -S(0)2NR2iR2 , - NR2iC(0)NR2i R2i”, -SR21 , - S(0)R2i, -S(0)2R2i, -CN, haloalkyl, haloalkoxy, -C(0)0R2i, -C(0)NR2iR2r, - OCH2CH2OR21, -NR2iS(0) ₂NR ₂rR2r and -C(CH ₃) ₂OR ₂I ; wherein R ₂₁, R _21' and R _21” are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound of general Formula (l ^a’)

wherein

X is selected from a bond, -[C(R _aRb)] _P-, -[CH ₂]pC(0)[CH ₂] _q-, -[CH ₂] _pC(0)N(R _z)[CH ₂] _q-, - [CH ₂] _pN(R _z)C(0)[CH ₂] _q- and -[CH ₂] _pN(R _z)[CH ₂] _q-;

R _a is selected from hydrogen, halogen, substituted or unsubstituted Ci- ₆ alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

R _b is selected from hydrogen, halogen, substituted or unsubstituted Ci- ₆ alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; alternatively, R _a and R _b, taken together with the carbon atom to which they are attached, may form a substituted or unsubstituted cycloalkyl;

R _z is selected from hydrogen, substituted or unsubstituted Ci- ₆ alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl and - C(0)-Ci-6 alkyl; p is 0, 1 , 2, 3, 4 or 5; q is 0, 1 , 2, 3, 4 or 5; n is 0 or 1 ;

wherein m is 0, 1 or 2; r is 0, 1 or 2;

Y is -CH ₂- or C=0;

Rs is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted alkylcycloalkyl;

Rs· is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

alternatively, R ₅ and R ₅·, taken together with the carbon atom to which they are attached, form a substituted or unsubstituted cycloalkyl; wherein the alkyl, alkenyl or alkynyl defined in R ₅ and R ₅· if substituted, is substituted with one or more substituent/s selected from -OR ₅₁, halogen, -CN, haloalkyl, haloalkoxy and -NRsiRsr;

wherein the cycloalkyl, as defined in R ₅, also in alkylcycloalkyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R _5I , -OR ₅₁, -NO2, -NR51R51', -NR _5iC(0)R ₅r, -NR5iS(0)2R5r, -S(0)2NR5iR5-r,

NR _5iC(0)NR ₅rR ₅r', -SR ₅₁ , -S(0)Rsi, -S(0) ₂R _SI , -CN, haloalkyl, haloalkoxy, - C(0)0R _5I , -C(0)NR _5i R ₅ , -OCH ₂CH ₂OR _5I , -NR _5iS(0) ₂NR ₅rR ₅r and -

C(CH3)20R5i; preferably selected from halogen, -R51, -OR51, -NR51R51', -CN, haloalkyl and haloalkoxy; wherein R ₅₁, Rsr and R ₅r are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

wherein the cycloalkyl, as defined in R ₅-R _5', if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R52, -OR52, -NO2, -NR52R52', - NR ₅₂C(0)R _52', -NR ₅₂S(0) ₂R52', -S(0) ₂NR ₅₂R52', - NR ₅₂C(0)NR _52'R _52”, -SR ₅₂ , - S(0)R52, -S(0)2R52, -CN, haloalkyl, haloalkoxy, -C(0)0Rs2, -C(0)NR ₅₂Rs2', - OCH2CH2OR52, -NR ₅₂S(0)2NR _52'R52” and -C(CH3)20R52; preferably selected from halogen, -R52, -OR52, -NR52R52', -CN, haloalkyl and haloalkoxy; wherein R ₅₂, R _52' and R _52” are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

R ₆ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl and -C(0)R7; wherein the alkyl, alkenyl or alkynyl defined in R6, if substituted, is substituted with one or more substituent/s selected from -OR ₆₁, halogen, -CN, haloalkyl, haloalkoxy and -NR61R6I'; wherein the cycloalkyl, aryl or heterocyclyl defined in R6, also in alkylcycloalkyl, alkylaryl and alkylheterocyclyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R61, -OR61, -NO2, -NR6iR6r, -NR6iC(0)R6r, - NR6iS(0)2R6r, -S(0) ₂NR _6iR ₆r, - NR6iC(0)NR6i'R6i”, -SR61 , -S(0)R6i, -S(0)2R6i, -CN, haloalkyl, haloalkoxy, -C(0)0R6i, -C(0)NR6iR6r, -OCH2CH2OR61, - NR6iS(0) ₂NR ₆rR6r and -C(CH3)20R6i; preferably selected from halogen, -R61, - OR61, -NR61R6I', -CN, haloalkyl and haloalkoxy; wherein R ₆₁, Rer and R6i” are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

R ₇ is selected from substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl; wherein the alkyl, alkenyl or alkynyl defined in R ₇, if substituted, is substituted with one or more substituent/s selected from -OR71, halogen, -CN, haloalkyl, haloalkoxy and -NR71R71'; wherein the cycloalkyl, aryl and heterocyclyl, as defined in R ₇, also in alkylcycloalkyl, alkylaryl and alkylheterocyclyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R ₇₁ , -OR ₇I , -NO ₂, -NR _7i R ₇r, - NR _7iC(0)R ₇r, -NR _7iS(0) ₂R ₇r, -S(0) ₂NR _7iR ₇r, - NR _7iC(0)NR ₇-rR ₇-r, -SR ₇I , - S(0)R ₇I , -S(0) ₂R ₇I , -CN, haloalkyl, haloalkoxy, -C(0)0R _7i, -C(0)NR _7iR ₇r, - 0CH ₂CH ₂0R _7I , -NR _7IS(0) ₂NR _7I R _7I” and -C(CH ₃) ₂0R _7I ; preferably selected from halogen, -R ₇I , -OR ₇I , -NR _7iR ₇r, -CN, haloalkyl and haloalkoxy; wherein R ₇I , R ₇r and R ₇r are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

Re is selected from hydrogen, halogen, substituted or unsubstituted Ci-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl and -ORsi;

Rs· is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; wherein the alkyl, alkenyl or alkynyl defined in Re or Re·, if substituted, is substituted with one or more substituent/s selected from -ORsi, halogen, -CN, haloalkyl, haloalkoxy and -NRsiRsr; wherein Rsi and Rsr are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

R ₃ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted alkylcycloalkyl; wherein, the alkyl, alkenyl or alkynyl defined in R ₃, if substituted, is substituted with one or more substituent/s selected from -OR ₃₁, halogen, -CN, haloalkyl, haloalkoxy and -NR31R31'; wherein the cycloalkyl in R ₃, also in alkylcycloalkyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R ₃₁, -OR31, -NO2, -NR31R31', -NR _3iC(0)R ₃r, -NR3iS(0)2R3r, -S(0)2NR3i R3r, - N R ₃₁ C(0)N R ₃₁ R _{31 "}, -SR ₃₁ , -S(0)R ₃I , -S(0) ₂R ₃I , -CN, haloalkyl, haloalkoxy, -C(0)0R3i, -C(0)NR3iR3r, -OCH2CH2OR31,

NR3iS(0) ₂NR ₃rR3r' and -C(CH3)20R3i; preferably selected from halogen, - R31, -OR31, -NR31R31', -CN, haloalkyl and haloalkoxy; wherein R ₃₁, R _31' and R _31” are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

R _3' is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl; wherein, the alkyl, alkenyl or alkynyl defined in R _3', if substituted, is substituted with one or more substituent/s selected from -OR ₃₂, halogen, -CN, haloalkyl, haloalkoxy and -NR32R32'; wherein R ₃₂ and R _32' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

R ₄ and R _4' are independently selected from halogen, -R ₄I , -OR ₄I , -NO ₂, -NR _4iR ₄r, - NR _4iC(0)R ₄r, -NR _4iS(0) ₂R ₄r, -S(0) ₂NR _4iR ₄r, -NR _4iC(0)NR ₄rR ₄-r, -SR ₄I , - S(0)R4i, -S(0)2R4i, -CN, haloalkyl, haloalkoxy, -C(0)0R4i, -C(0)NR4iR4r, - OCH2CH2OR41, -NR4iS(0) ₂NR ₄rR4r and -C(CH3)20R4i; wherein R ₄₁, R ₄rand R ₄r are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl and substituted or unsubstituted cycloalkyl;

Rg and Rg· are independently selected from halogen, -R21, -OR21, -NO2, -NR21R21', - NR _2iC(0)R ₂r, -NR2iS(0)2R2r, -S(0)2NR2iR2r, - NR2iC(0)NR2i R2i”, -SR21 , - S(0)R2i, -S(0)2R2i, -CN, haloalkyl, haloalkoxy, -C(0)0R2i, -C(0)NR2iR2r, - OCH2CH2OR21, -NR2iS(0) ₂NR ₂rR2r' and -C(CH ₃) ₂OR ₂I ; wherein R21, R21' and R21” are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

the alkyl, alkenyl or alkynyl, also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, if substituted and the substitution has not been defined otherwise, it is substituted with one or more substituent/s selected from =0, -OR ₁₃, halogen, -CN, haloalkyl, haloalkoxy and -NR13R13'; wherein R ₁₃ and R _13' are independently selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl, and unsubstituted C _2-6 alkynyl;

the aryl, heterocyclyl or cycloalkyl, also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, if substituted and the substitution has not been defined otherwise, it is substituted with one or more substituent/s selected from =0, halogen, -R-u, -OR14, -NO2, -NR14R14', -NRl ₄C(0)Rl4', -NRl4S(0)2Rl4’, -S(0) ₂NRl ₄Rl4',

NRi ₄C(0)NRi4'Ri4”, -SR14 , -S(0)Ri4, -S(0)2Ri4, -CN, haloalkyl, haloalkoxy, - C(0)0Ri4, -C(0)NRi ₄Ri4', -OCH2CH2OR14, -NRi ₄S(0) ₂NRi4'Ri4” and -C(CH3)20R-i4; wherein R-u, R-i ₄ and R-u- are independently selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl, unsubstituted C _2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl;

optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound of general Formula (l ^b)

wherein R1, R3, R3', R ₄, R ₄·, R9, Rg·, X, Ui, Y2 and n are as defined below in the detailed description, optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof. In a further embodiment the compound according to the invention of general Formula (I) is a compound of general Formula (l ^b)

wherein X is selected from a bond, -[C(R _aRb)] _P-, -[CH ₂]pC(0)[CH ₂] _q-, -[CH ₂] _pC(0)N(R _z)[CH ₂] _q-, - [CH ₂] _pN(R _z)C(0)[CH ₂] _q- and -[CH ₂] _pN(R _z)[CH ₂] _q-;

R _a is selected from hydrogen, halogen, substituted or unsubstituted Ci- ₆ alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; R _b is selected from hydrogen, halogen, substituted or unsubstituted Ci- ₆ alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; alternatively, R _a and R _b, taken together with the carbon atom to which they are attached, may form a substituted or unsubstituted cycloalkyl; R _z is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl and - C(0)-Ci-6 alkyl; p is 0, 1 , 2, 3, 4 or 5; q is 0, 1 , 2, 3, 4 or 5;

n is 0 or 1 ;

Yi is -C(RioRio')-; wherein R ₁₀ and Rio· are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; alternatively, R ₁₀ and Rio· may form, with the carbon atom to which they are attached, a substituted or unsubstituted cycloalkyl;

Y ₂ is -C(Rio”Rio )-; wherein Rio- and R-io- are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; alternatively, R _10” and Rio- may form, with the carbon atom to which they are attached, a substituted or unsubstituted cycloalkyl;

wherein m is 0, 1 or 2; r is 0, 1 or 2;

Y is -CH ₂- or C=0;

R ₅ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted alkylcycloalkyl;

Re· is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

alternatively, R ₅ and R ₅·, taken together with the carbon atom to which they are attached, form a substituted or unsubstituted cycloalkyl;

R ₆ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl and -C(0)R7;

R ₇ is selected from substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl;

Re is selected from hydrogen, halogen, substituted or unsubstituted Ci-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl and -ORsi;

Rs· is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; wherein Rei is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

R ₃ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted alkylcycloalkyl;

R _3' is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

R ₄ and R _4' are independently selected from halogen, -R ₄I , -OR ₄I , -NO ₂, -NR _4iR ₄r, - NR _4iC(0)R ₄r, -NR _4iS(0) ₂R ₄r, -S(0) ₂NR _4iR ₄r, -NR _4iC(0)NR ₄rR ₄-r, -SR ₄I , - S(0)R _4I , -S(0) ₂R _4I , -CN, haloalkyl, haloalkoxy, -C(0)0R _4i, -C(0)NR _4iR ₄r, - 0CH ₂CH ₂0R _4I , -NR _4iS(0) ₂NR _{4i '}R _4i” and -C(CH ₃) ₂0R _4I ; wherein R _4I , R ₄rand R ₄r are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl and substituted or unsubstituted cycloalkyl;

Rg and Rg· are independently selected from halogen, -R21, -OR21, -NO2, -NR21R21', - NR _2iC(0)R ₂r, -NR2iS(0)2R2 , -S(0)2NR2iR2 , - NR2iC(0)NR2i R2i”, -SR21 , - S(0)R2i, -S(0)2R2i, -CN, haloalkyl, haloalkoxy, -C(0)0R2i, -C(0)NR2iR2r, - OCH2CH2OR21, -NR2iS(0) ₂NR ₂rR2r' and -C(CH ₃) ₂OR ₂I ; wherein R ₂₁, R ₂r and R _21” are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, and substituted or unsubstituted C2-6 alkynyl;

optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound of general Formula (l ^b)

wherein

X is selected from a bond, -[C(R _aRb)] _P-, -[CH ₂]pC(0)[CH ₂] _q-, -[CH ₂] _pC(0)N(R _z)[CH ₂] _q-, - [CH ₂] _pN(R _z)C(0)[CH ₂] _q- and -[CH ₂] _pN(R _z)[CH ₂] _q-;

R _a is selected from hydrogen, halogen, substituted or unsubstituted Ci- ₆ alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

R _b is selected from hydrogen, halogen, substituted or unsubstituted Ci- ₆ alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; alternatively, R _a and R _b, taken together with the carbon atom to which they are attached, may form a substituted or unsubstituted cycloalkyl;

R _z is selected from hydrogen, substituted or unsubstituted Ci- ₆ alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl and - C(0)-Ci-6 alkyl; p is 0, 1 , 2, 3, 4 or 5; q is 0, 1 , 2, 3, 4 or 5; n is 0 or 1 ;

Yi is -C(RioRio')-; wherein R ₁₀ and Rio· are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; alternatively, R ₁₀ and Rio· may form, with the carbon atom to which they are attached, a substituted or unsubstituted cycloalkyl;

Y2 is -C(Rio”Rio'”)-; wherein Rio- and R-io- are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; alternatively, R _10” and Rio- may form, with the carbon atom to which they are attached, a substituted or unsubstituted cycloalkyl;

wherein m is 0, 1 or 2; r is 0, 1 or 2;

Y is -CH2- or C=0;

R ₅ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted alkylcycloalkyl;

Re· is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

alternatively, R ₅ and Rs·, taken together with the carbon atom to which they are attached, form a substituted or unsubstituted cycloalkyl;

wherein the alkyl, alkenyl or alkynyl defined in R ₅ and R ₅· if substituted, is substituted with one or more substituent/s selected from -OR ₅₁, halogen, -CN, haloalkyl, haloalkoxy and -NRsiRsr;

wherein the cycloalkyl, as defined in R ₅, also in alkylcycloalkyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R ₅₁, -OR ₅₁, -NO2, -NR51R51', -NR _5iC(0)R _5r, -NR5iS(0)2R5r, -S(0)2NR5iR5-r,

NR _5iC(0)NR ₅rR ₅r', -SR ₅₁ , -S(0)Rsi, -S(0) ₂R _SI , -CN, haloalkyl, haloalkoxy, - C(0)0R ₅I , -C(0)NR _5i R ₅ , -OCH ₂CH ₂OR ₅I , -NR _5iS(0) ₂NR ₅rR _5i and -

C(CH3)20R5i; preferably selected from halogen, -R51, -OR51, -NR51R51', -CN, haloalkyl and haloalkoxy; wherein R ₅₁, Rsr and Rsr are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl; wherein the cycloalkyl, as defined in R5-R5', if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R52, -OR52, -NO2, -NR52R52', - NR ₅₂C(0)R _52', -NR ₅₂S(0) ₂R52', -S(0) ₂NR ₅₂R52', - NR ₅₂C(0)NR _52'R _52”, -SR ₅₂ , - S(0)R52, -S(0)2R52, -CN, haloalkyl, haloalkoxy, -C(0)0Rs2, -C(0)NR ₅₂R52·, - OCH2CH2OR52, -NR ₅₂S(0)2NR _52'R52” and -C(CH3)20R52; preferably selected from halogen, -R52, -OR52, -NR52R52', -CN, haloalkyl and haloalkoxy; wherein R52, R52' and R52” are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, and substituted or unsubstituted C2-6 alkynyl;

R ₆ is selected from hydrogen, substituted or unsubstituted Ci- ₆ alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl and -C(0)R7; wherein the alkyl, alkenyl or alkynyl defined in R ₆, if substituted, is substituted with one or more substituent/s selected from -OR61, halogen, -CN, haloalkyl, haloalkoxy and -NR61R6I'; wherein the cycloalkyl, aryl or heterocyclyl defined in R ₆, also in alkylcycloalkyl, alkylaryl and alkylheterocyclyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R61, -OR61, -NO2, -NR6iR6r, -NR6iC(0)R6r, - NR6iS(0)2R6r, -S(0) ₂NR _6iR ₆r, - NR6iC(0)NR6i'R6i”, -SR61 , -S(0)R6i, -S(0)2R6i, -CN, haloalkyl, haloalkoxy, -C(0)0R6i, -C(0)NR6iR6r, -OCH2CH2OR61, - NR6iS(0) ₂NR ₆rR6r' and -C(CH3)20R6i; preferably selected from halogen, -R61, - OR61, -NR61R6I', -CN, haloalkyl and haloalkoxy; wherein R ₆₁, Rer and R6r are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

R ₇ is selected from substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted alkylaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylheterocyclyl; wherein the alkyl, alkenyl or alkynyl defined in R ₇, if substituted, is substituted with one or more substituent/s selected from -OR ₇₁, halogen, -CN, haloalkyl, haloalkoxy and -NR71R71'; wherein the cycloalkyl, aryl and heterocyclyl, as defined in R ₇, also in alkylcycloalkyl, alkylaryl and alkylheterocyclyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R71, -OR71, -NO2, -NR _7i R ₇r, - NR _7iC(0)R ₇r, -NR7iS(0)2R7 , -S(0)2NR7iR7r, - NR7iC(0)NR7-rR7-r, -SR71 , - S(0)R7i, -S(0)2R7i, -CN, haloalkyl, haloalkoxy, -C(0)0R7i, -C(0)NR _7iR7r, - OCH2CH2OR71, -NR7iS(0) ₂NR ₇rR7r' and -C(CH3)20R7i; preferably selected from halogen, -R71, -OR71, -NR71R71', -CN, haloalkyl and haloalkoxy; wherein R ₇₁, R ₇r and R ₇r are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

Re is selected from hydrogen, halogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl and -ORsi; Rs· is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl; wherein the alkyl, alkenyl or alkynyl defined in Re or Re·, if substituted, is substituted with one or more substituent/s selected from -ORs-i, halogen, -CN, haloalkyl, haloalkoxy and -NRe-iRsr; wherein Rei and Rsr are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl;

R3 is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted alkylcycloalkyl; wherein, the alkyl, alkenyl or alkynyl defined in R3, if substituted, is substituted with one or more substituent/s selected from -OR31 , halogen, -CN, haloalkyl, haloalkoxy and -N R31 R31'; wherein the cycloalkyl in R ₃, also in alkylcycloalkyl, if substituted, is substituted with one or more substituent/s selected from =0, halogen, -R ₃₁, -OR31, -NO2, -NR31R31', -NR _3iC(0)R ₃r, -NR3iS(0)2R3r, -S(0)2NR3i R3r, - N R31 C(0)N R31 R31 ", -SR31 , -S(0)R ₃I , -S(0) ₂R ₃I , -CN, haloalkyl, haloalkoxy, -C(0)0R3i, -C(0)NR3iR3r, -OCH2CH2OR31,

NR3iS(0) ₂NR ₃rR3r' and -C(CH3)20R3i; preferably selected from halogen, - R31, -OR31, -NR31R31', -CN, haloalkyl and haloalkoxy; wherein R ₃₁, R _31' and R _31” are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl; R ₃· is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl; wherein, the alkyl, alkenyl or alkynyl defined in R ₃·, if substituted, is substituted with one or more substituent/s selected from -OR ₃₂, halogen, -CN, haloalkyl, haloalkoxy and -NR ₃₂R ₃₂·; wherein R ₃₂ and R ₃₂· are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

R ₄ and R _4' are independently selected from halogen, -R ₄I , -OR ₄I , -NO2, -NR _4iR ₄r, - NR _4iC(0)R ₄r, -NR _4iS(0) ₂R ₄r, -S(0) ₂NR _4iR ₄r, -NR _4iC(0)NR ₄rR ₄-r, -SR ₄I , - S(0)R ₄I , -S(0) ₂R ₄I , -CN, haloalkyl, haloalkoxy, -C(0)0R _4i, -C(0)NR _4iR ₄r, - 0CH ₂CH ₂0R ₄I , -NR _4iS(0) ₂NR _{4i '}R _4i” and -C(CH ₃) ₂0R ₄I ; wherein R ₄I , R ₄rand R ₄rare independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl and substituted or unsubstituted cycloalkyl;

Rg and Rg· are independently selected from halogen, -R21, -OR21, -NO2, -NR21R21', - NR _2iC(0)R ₂r, -NR2iS(0)2R2 , -S(0)2NR2iR2 , - NR2iC(0)NR2i R2i”, -SR21 , - S(0)R2i, -S(0)2R2i, -CN, haloalkyl, haloalkoxy, -C(0)0R2i, -C(0)NR2iR2r, - OCH2CH2OR21, -NR2iS(0) ₂NR ₂rR2r' and -C(CH ₃) ₂OR ₂I ; wherein R ₂₁, R _21' and R _21” are independently selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, and substituted or unsubstituted C2-6 alkynyl;

the alkyl, alkenyl or alkynyl, also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, if substituted and the substitution has not been defined otherwise, it is substituted with one or more substituent/s selected from =0, -OR ₁₃, halogen, -CN, haloalkyl, haloalkoxy and -NR13R13'; wherein R ₁₃ and R _13' are independently selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl, and unsubstituted C _2-6 alkynyl;

the aryl, heterocyclyl or cycloalkyl, also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, if substituted and the substitution has not been defined otherwise, it is substituted with one or more substituent/s selected from =0, halogen, -R-u, -OR-u, -NO2, -NR14R14', -NRl ₄C(0)Rl4·, -NRl4S(0)2Rl4’, -S(0) ₂NRl ₄Rl4', NRi ₄C(0)NRi4'Ri4”, -SR14 , -S(0)Ri4, -S(0)2Ri4, -CN, haloalkyl, haloalkoxy, -

C(0)0Ri4, -C(0)NRi ₄Ri4', -OCH2CH2OR14, -NRi ₄S(0) ₂NRi4'Ri4” and -C(CH3)20R-i4; wherein R ₁₄, Ri _b and R-u- are independently selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl, unsubstituted C _2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl;

optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound of general Formula (l ^b’)

(l ^b ), wherein Ri, R3, R3', R ₄, R ₄·, R9, RET, X and n are as defined below in the detailed description, optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.

In a further embodiment the compound according to the invention of general Formula (I) is a compound of general Formula (l ^b’)

(l ^b' wherein

X is selected from a bond, -[C(R _aRb)] _P-, -[CH ₂]pC(0)[CH ₂] _q-, -[CH ₂] _pC(0)N(R _z)[CH ₂] _q-, - [CH ₂] _pN(R _z)C(0)[CH ₂] _q- and -[CH ₂] _pN(R _z)[CH ₂] _q-;

R _a is selected from hydrogen, halogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

R _b is selected from hydrogen, halogen, substituted or unsubstituted C alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; alternatively, R _a and R _b, taken together with the carbon atom to which they are attached, may form a substituted or unsubstituted cycloalkyl;

R _z is selected from hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl and - C(0)-Ci-6 alkyl; p is 0, 1 , 2, 3, 4 or 5; q is 0, 1 , 2, 3, 4 or 5;